The goal is to define the significance of pancreatic acinar cell hyperplastic nodules and adenomas in F344 rats. Such lesions have been reported in F344 rats that were given corn oil by gavage as part of bioassay studies of the National Toxicology Program. They are similar to lesions that develop in carcinogen-treated rats and also occur spontaneously in aged rats. Experiments are proposed that will compare the development of such lesions in rats that are given corn oil by gavage and in rats that are given a similar amount of corn oil mixed in the diet. Subsequent studies will compare the incidence and rate of growth of proliferative acinar cell lesions in groups of rats that are treated with varying levels of corn oil in both carcinogen-treated and untreated rats. Other fats with varying degrees of unsaturation (including olive oil) will be compared in regard to their effect on the incidence and growth of the pancreatic lesions. The effect of varying levels of intake of corn oil and other unsaturated fats on the plasma levels of CCK will be determined--since CCK is a known trophic hormone for the pancreas. The fatty acid and diglyceride composition of adipose tissue and pancreas will be determined in selected groups of rats to see if a critical change can be identified that correlates with enhanced development of the proliferative acinar cell lesions. The potential of various sizes and histologic types of proliferative acinar cell lesions for growth in culture and for transplantation will be assessed. Ability to grow in soft agar and oncogenicity of cells transplanted into syngeneic hosts will be taken as evidence of neoplastic transformation. The ability of DNA from selected lesions to transform NIH 3T3 cells by transfection will be assessed and the potential transforming gene(s) identified. The expression of specific oncogenes will be probed in transplantable tumors, and in selected large, non-transplantable lesions. The growth potential of similar lesions from two strains of rats (Lewis and F344) will be compared as will lesions induced by three known pancreatic carcinogens, azaserine, N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, and 4-hydroxyaminoquinoline-1-oxide and spontaneous lesions from 2-year-old F344 rats.